NM_014140.3(SMARCAL1):c.506A>G (p.Lys169Arg) AND Schimke immuno-osseous dysplasia

Clinical significance:Uncertain significance (Last evaluated: Oct 19, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_014140.3(SMARCAL1):c.506A>G (p.Lys169Arg)]

NM_014140.3(SMARCAL1):c.506A>G (p.Lys169Arg)

SMARCAL1:SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a like 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_014140.3(SMARCAL1):c.506A>G (p.Lys169Arg)
  • NC_000002.12:g.216415210A>G
  • NG_009771.1:g.7797A>G
  • NM_001127207.2:c.506A>G
  • NM_014140.3:c.506A>G
  • NP_001120679.1:p.Lys169Arg
  • NP_054859.2:p.Lys169Arg
  • LRG_108t1:c.506A>G
  • LRG_108:g.7797A>G
  • LRG_108p1:p.Lys169Arg
  • NC_000002.11:g.217279933A>G
Protein change:
dbSNP: rs777999697
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_001127207.2:c.506A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_014140.3:c.506A>G - missense variant - [Sequence Ontology: SO:0001583]


Schimke immuno-osseous dysplasia (SIOD)
Spondyloepiphyseal dysplasia nephrotic syndrome; Schimke syndrome; Schimke immunoosseous dysplasia
MONDO: MONDO:0009458; MedGen: C0877024; Orphanet: 1830; OMIM: 242900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV001415007Invitaecriteria provided, single submitter
Uncertain significance
(Oct 19, 2020)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing



Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

Details of each submission

From Invitae, SCV001415007.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)


This sequence change replaces lysine with arginine at codon 169 of the SMARCAL1 protein (p.Lys169Arg). The lysine residue is weakly conserved and there is a small physicochemical difference between lysine and arginine. This variant is present in population databases (rs777999697, ExAC 0.05%). This variant has not been reported in the literature in individuals with SMARCAL1-related disease. ClinVar contains an entry for this variant (Variation ID: 497427). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: Tolerated; PolyPhen-2: Benign; Align-GVGD: Class C0. The arginine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 7, 2021

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